2sxl
From Proteopedia
SEX-LETHAL RBD1, NMR, MINIMIZED AVERAGE STRUCTURE
Structural highlights
Function[SXL_DROME] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Sex-lethal (Sxl) protein from Drosophila melanogaster has two RNA-binding domains (RBDs). As the amino-terminal RBD (RBD1) of the Sxl protein exhibits low sequence homology to the typical RBDs, particularly at the putative functional residues, it was difficult to unambiguously locate the RNP1 and RNP2 motifs. Therefore, in the present study, we defined the amino and carboxy-terminal borders of the first RNA-binding domain (RBD1) of the Sxl protein by limited tryptic digestion. By replacement of Phe166 by Tyr, we constructed a highly soluble mutant, which exhibits the same RNA-binding properties as those of the wild-type. Using this mutant protein, we performed NMR measurements, and elucidated the secondary and tertiary structures of the Sxl RBD1 in solution. The betaalphabetabetaalphabeta folding pattern is conserved in the solution structure of the Sxl RBD1, as in other reported RBD structures. This allowed us to identify both the RNP1 and RNP2 motifs of the Sxl RBD1 unambiguously. Intriguingly, the RNP2 motif of the Sxl RBD1 has an Ile residue at the second position, which is generally occupied by an aromatic amino acid residue in RBDs and has been suggested to be involved in their RNA binding. Furthermore, the loop region between beta2 and beta3 of the Sxl RBD1 has an exceptional cluster of aromatic amino acid residues, in place of the normal basic amino acid cluster. In contrast, the second RBD of Sxl does not exhibit these characteristic features. A characteristic arrangement of aromatic amino acid residues in the solution structure of the amino-terminal RNA-binding domain of Drosophila sex-lethal.,Inoue M, Muto Y, Sakamoto H, Kigawa T, Takio K, Shimura Y, Yokoyama S J Mol Biol. 1997 Sep 12;272(1):82-94. PMID:9299339[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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